A synthetic ion transporter that disrupts autophagy and induces apoptosis by perturbing cellular chloride concentrations

Busschaert, Nathlie, Park, Seong-Hyun, Baek, Kyung-Hwa, Choi, Yoon Pyo, Park, Jinhong, Howe, Ethan N.W., Hiscock, Jennifer R., Karagiannidis, Louise E., Marques, Igor, Félix, Vítor, and others. (2017) A synthetic ion transporter that disrupts autophagy and induces apoptosis by perturbing cellular chloride concentrations. Nature Chemistry, 9 . pp. 667-675. ISSN 1755-4330. (doi:10.1038/nchem.2706) (KAR id:60009)

PDF Author's Accepted Manuscript Language: English
Download this file (PDF/1MB)	Preview
Request a format suitable for use with assistive technology e.g. a screenreader
Microsoft Word Author's Accepted Manuscript Language: English
Download this file (Microsoft Word/8MB)
Request a format suitable for use with assistive technology e.g. a screenreader
Official URL: http://dx.doi.org/10.1038/nchem.2706

Abstract

Perturbations in cellular chloride concentrations can affect cellular pH, autophagy and lead to the onset of apoptosis. With this in mind synthetic ion transporters have been used to disturb cellular ion homeostasis and thereby induce cell death; however, it is not clear whether synthetic ion transporters can also be used to disrupt autophagy. Here we show that squaramide-based ion transporters enhance the transport of chloride anions in liposomal models and promote sodium chloride influx into the cytosol. Liposomal and cellular transport activity of the squaramides is shown to correlate with cell death activity, which is attributed to caspase-dependent apoptosis. One ion transporter was also shown to cause additional changes in the lysosomal pH which leads to impairment of lysosomal enzyme activity and disruption of autophagic processes. This disruption is independent of the initiation of apoptosis by the ion transporter. This study provides the first experimental evidence that synthetic ion transporters can disrupt both autophagy and induce apoptosis.

Item Type:	Article
DOI/Identification number:	10.1038/nchem.2706
Uncontrolled keywords:	Functional Materials Group, squaramide, supramolecular chemistry, apoptosis, ion transport, autophagy
Subjects:	Q Science > QD Chemistry
Divisions:	Divisions > Division of Natural Sciences > Physics and Astronomy
Depositing User:	Michael Woods
Date Deposited:	26 Jan 2017 10:51 UTC
Last Modified:	05 Nov 2024 10:52 UTC
Resource URI:	https://kar.kent.ac.uk/id/eprint/60009 (The current URI for this page, for reference purposes)

University of Kent Author Information

Hiscock, Jennifer R..

Creator's ORCID:	https://orcid.org/0000-0002-1406-8802
CReDIT Contributor Roles:

Depositors only (login required):

Altmetric

Download Statistics

Total unique views for this document in KAR since July 2020. For more details click on the image.